NM_014912.5:c.-11-8462C>T

Variant names:

• chr10-92248823-G-A
• rs11186872
• NM_014912.5:c.-11-8462C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014912.5(CPEB3):​c.-11-8462C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,042 control chromosomes in the GnomAD database, including 7,975 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (7975 hom., cov: 32)
• Consequence: CPEB3 NM_014912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 4 publications found

Genes affected

CPEB3 (HGNC:21746): (cytoplasmic polyadenylation element binding protein 3) Enables mRNA 3'-UTR binding activity and translation factor activity, RNA binding. Involved in cellular response to amino acid stimulus; negative regulation of transcription by RNA polymerase II; and positive regulation of mRNA catabolic process. Located in several cellular components, including cytosol; midbody; and nucleoplasm. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]

CPEB3 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014912.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPEB3	NM_014912.5	MANE Select	c.-11-8462C>T		intron	N/A	NP_055727.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPEB3	ENST00000265997.5	TSL:1 MANE Select	c.-11-8462C>T		intron	N/A	ENSP00000265997.4	Q8NE35-1
	CPEB3	ENST00000903868.1		c.-11-8462C>T		intron	N/A	ENSP00000573927.1
	CPEB3	ENST00000903866.1		c.-11-8462C>T		intron	N/A	ENSP00000573925.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48172 AN: 151924 Hom.: 7971 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.338

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.317 AC: 48208 AN: 152042 Hom.: 7975 Cov.: 32 AF XY: 0.317 AC XY: 23561 AN XY: 74338

African (AFR) AF: 0.344 AC: 14237 AN: 41446

American (AMR) AF: 0.432 AC: 6600 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2124 AN: 5174

South Asian (SAS) AF: 0.310 AC: 1495 AN: 4824

European-Finnish (FIN) AF: 0.245 AC: 2587 AN: 10570

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19090 AN: 67968

Other (OTH) AF: 0.339 AC: 717 AN: 2114

Alfa AF: 0.298 Hom.: 20564

Bravo AF: 0.336

Asia WGS AF: 0.348 AC: 1213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.4
DANN	Benign	0.68
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11186872; hg19: chr10-94008580;